DETAILED ACTION
Claims 6-11 are currently pending in the instant application.
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Response to Amendment/Arguments
Applicant’s amendments and arguments in a response filed 08/03/2026 have been fully considered and entered into the application. Applicant has overcome
The 35 U.S.C. 112(a) rejection of claims 6-11 in view of Applicant’s amendment to claim 6.
Applicant argues that Gupta teaches variety of individual lipid-lowering agents and respective clinical development status and does not teach or suggest combining the agents with one another for therapeutic use. Specifically Gupta teaches bempedoic acid and pemafibrate in combination therapy with statins and there is no motivation to combine bempedoic acid with pemafibrate. Applicant argues that Gupta discloses bempedoic acid and pemafibrate as alternative members of a group without guidance towards combined use in the prior art. However as stated in the prior rejection, MPEP 2144.06, Section I states that it is obvious to combine equivalents known for the same purpose. "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted) (Claims to a process of preparing a spray-dried detergent by mixing together two conventional spray-dried detergents were held to be prima facie obvious.). (That the two claimed types of active agents, GABA-a agonists and ARBs, were known to be useful for the same purpose—alleviating hypertension—alone can serve as a motivation to combine). In the instant case, both bempedoic acid and pemafibrate are taught as active ingredients for lowering lipids. Specifically, bempedoic acid is taught in treatment of hypercholesteremia and mixed dyslipidemias and pemafibrate is used for dyslipidemia with a reduction in triglycerides. MPEP 2144.06, Section II also states that “additionally, an express suggestion to substitute one equivalent component or process for another is not necessary to render such substitution obvious. In reFout, 675 F.2d 297, 213 USPQ 532 (CCPA 1982)”. Both bempedoic acid and pemafibrate are taught to as components and active ingredients to treat hypercholesterolemia or hypertriglyceridemia as well as for lowering the risk of atherosclerotic cardiovascular disease in the prior art. Although the prior art does not exemplify a single composition having bempedoic acid and pemafibrate, the prior art of Gupta teaches compositions having bempedoic acid (see p. 613-614) and pembafibrate (see p. 614) as an active component (see claim 5, p. 292).
Applicant argues that Examples 1-3 show combination comprising pemafibrate and bempedoic acid as to what would have been expected from individual agents and synergistic effects were observed. According to Examples 1-3, it appears that the combination of pemafibrate and bempedoic acid improve dyslipidemia. However, claim 6 is drawn to treating any cardiovascular disease comprising administering an effective amount of a PPARα agonist and ACL inhibitor. According to MPEP 716.02(d), whether the unexpected results are the result of unexpectedly improved results or a property not taught by the prior art, the “objective evidence of nonobviousness must be commensurate in scope with the claims which the evidence is offered to support.” In other words, the showing of unexpected results must be reviewed to see if the results occur over the entire claimed range. In re Clemens, 622 F.2d 1029, 1036, 206 USPQ 289, 296 (CCPA 1980). Given the breadth of compounds and agents encompassed by the term PPARα agonist and ACL inhibitor and that Applicant has only shown unexpected results for one species of each and that this combination improves dyslipidemia, one cannot extrapolate those results to the entire breadth of the claims.
Regarding the Applicant’s arguments over Zhang, Applicant argues that Zhang does not teach or suggest the use of a combination comprising PPARα agonist and ACL inhibitor for treatment of dyslipidemia or cardiovascular disease. Although Zhang teaches method of treating metabolic, cardiovascular and inflammatory disorders through administration of a glycine or glycine-containing tripeptide molecule, the instant claims do not preclude using glycine or glycine-containing tripeptide molecule as said the instant methods are taught to administer compositions comprising a PPARα agonist and ACL inhibitor. Further, although Zhang teaches broadly that a secondary therapeutic agent may be administered, the PPARα agonist and ACL inhibitor are still taught. Applicant alleges that selection from a laundry list would not support a conclusion of obviousness. However when a person of ordinary skill is faced with “a finite number of identified, predictable solutions” to a problem and pursues “the known options within his or her technical grasp,” the resulting discovery “is likely the product not of innovation but of ordinary skill and common sense.” KSR, 127 S. Ct. at 1742. So too, “[g]ranting patent protection to advances that would occur in the ordinary course without real innovation retards progress.” Id. at 1741. In other cases, though, researchers can only “vary all parameters or try each of numerous possible choices until one possibly arrive[s] at a successful result, where the prior art [gives] either no indication of which parameters [are] critical or no direction as to which of many possible choices is likely to be successful.” In re O'Farrell, 853 F.2d 894, 903 [7 USPQ2d 1673] (Fed. Cir. 1988). In such cases, “courts should not succumb to hindsight claims of obviousness.” In re Kubin, 561 F.3d 1351, No. 2008-1184, slip op. at 14 [90 USPQ2d 1417] (Fed. Cir. Apr. 3, 2009).
In the instant case, Zhang teaches both bempedoic acid and pemafibrate as active ingredients in the treating a metabolic disease and/or cardiovascular disease, wherein a metabolic and cardiovascular disease includes arteriosclerosis, hyperlipidemia which may be hypertriglyceridemia or hypercholesterolemia. Thus, since Zhang teaches both ingredients for treating said diseases and there is no indication that administering said compounds together would be expected to be detrimental or result in the compositions not possessing the prior art utility, researchers can vary all parameters and the courts should not succumb to hindsight claims of obviousness. MPEP 2144.06, Section II also states that “additionally, an express suggestion to substitute one equivalent component or process for another is not necessary to render such substitution obvious. In reFout, 675 F.2d 297, 213 USPQ 532 (CCPA 1982)”. Both bempedoic acid and pemafibrate are taught to as components and active ingredients to treat hypercholesterolemia or hypertriglyceridemia as well as for lowering the risk of atherosclerotic cardiovascular disease in the prior art. MPEP 2144.06, Section II also states that “additionally, an express suggestion to substitute one equivalent component or process for another is not necessary to render such substitution obvious. In reFout, 675 F.2d 297, 213 USPQ 532 (CCPA 1982)”. Both bempedoic acid and pemafibrate are taught to as components and active ingredients to treat hypercholesterolemia or hypertriglyceridemia as well as for lowering the risk of atherosclerotic cardiovascular disease in the prior art. Although the prior art does not exemplify a single composition having bempedoic acid and pemafibrate, the prior art of Zhang teaches compositions having bempedoic acid and pembafibrate as an active components.
Applicant argues that the Examiner has relied on impermissible hindsight in applying the prior art of Zhang since there is no specific motivation to combine the particular agents from the disclosed possibilities, let alone a PPARα agonist and ACL inhibitor of the instant claims. In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971).
Regarding Applicant’s arguments that Example 1-3 the combination of pemafibrate and bempedoic acid exhibit synergistic effects, according to MPEP 716.02(d), whether the unexpected results are the result of unexpectedly improved results or a property not taught by the prior art, the “objective evidence of nonobviousness must be commensurate in scope with the claims which the evidence is offered to support.” In other words, the showing of unexpected results must be reviewed to see if the results occur over the entire claimed range. In re Clemens, 622 F.2d 1029, 1036, 206 USPQ 289, 296 (CCPA 1980). Given the breadth of compounds and agents encompassed by the term PPARα agonist and ACL inhibitor and that Applicant has only shown unexpected results for one species of each and that this combination improves dyslipidemia, one cannot extrapolate those results to the entire breadth of the claims.
As a result, the 35 U.S.C. 103 rejections have been maintained.
Maintained Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claim(s) 6-11 is/are rejected under 35 U.S.C. 103 as being unpatentable over Gupta et al (see Expert Opinion on Investigational Drugs, 2020, Vol. 29, No. 6, p. 611-622, reference cited in IDS filed 10/20/2023).
Gupta et al teaches reduction of low-density lipoprotein cholesterol (LDL-C) further translates into lowering of cardiovascular mortality and that combination strategies could improve outcomes (see abstract, p. 611). Currently primary approach for management and prevention of atherosclerotic cardiovascular disease (AVCVD) targets low-density lipoprotein (LDL) cholesterol (LDL-C). Lowering of LDL-C has been shown to be effective in lowering the risk of ASCVD in dose-dependent manner (see p. 611). Further Gupta et al teach that lipid metabolism is the natural area to seek improvements as it has the clearest and best studied atherosclerotic mechanisms. In particular, bempedoic acid, which corresponds to 8-hydroxy-2,2,14, 14-tetramethylpentadecanedioic acid (the compound of instant claim 10), blocks ACL enzyme and is used for treatment of hypercholesteremia and mixed dyslipidemias (see Section 5.1. Bempedoic acid, p. 613-614). Further pemafibrate, which corresponds to (R)-2-[3-[[N-(benzoxazole-2-yl)-N-3-(4-methoxyphenoxy)propyl]aminomethyl]phenoxy]butyric acid (the compound of instant claim 9), is a PPAR nuclear receptor that binds to DNA and is used for dyslipidemia with a reduction in triglycerides (TGs). Further, Gupta et al teach pembafibrate used in studies for atherogenesis prevention (see p. 614, Section 5.2. Pemafibrate). Gupta teaches that statins are cornerstone therapy for primary and secondary ASCVD prevention but for patients who are intolerant to statins, other options such as bempedoic acid, pemafibrate shown to reduce LDL-C or TGs (see Table 1, p. 617) are being studied and developed. Bempedoic acid is taught specifically as a newer hypolipidemic drug and clinicians can now decide which drug combination would be an optimal lipid management strategy (see p. 619, expert opinion).
Thus, prior to the filing of the instant application, following the teachings of Gupta et al would have been prima facie obvious to combine the compounds bempedoic acid and pemafibrate in order to treat hypercholesterolemia or hypertriglyceridemia as well as for lowering the risk of atherosclerotic cardiovascular disease. MPEP 2144.06, Section I states that it is obvious to combine equivalents known for the same purpose. "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted) (Claims to a process of preparing a spray-dried detergent by mixing together two conventional spray-dried detergents were held to be prima facie obvious.). (That the two claimed types of active agents, GABA-a agonists and ARBs, were known to be useful for the same purpose—alleviating hypertension—alone can serve as a motivation to combine). In the instant case, both bempedoic acid and pemafibrate are taught for treatment of hypercholesteremia and reduction in triglycerides, leading to potential decreased risk of atherosclerotic cardiovascular disease.
Claim(s) 6-11 is/are rejected under 35 U.S.C. 103 as being unpatentable over Zhang et al (see WIPO Pub No. 2020/033919, pub. 02/13/2020 and filed 08/09/2019, claiming priority to US Prov. No. 62/717,546, filed 08/10/2018, hereafter referred to as WO ‘919, reference cited in IDS filed 10/20/2023). WO ‘919 teaches a method for treating a metabolic disease and/or cardiovascular disease, wherein a metabolic and cardiovascular disease includes arteriosclerosis, hyperlipidemia which may be hypertriglyceridemia or hypercholesterolemia by administering a glycine or glycine-containing tripeptide molecule to a subject (see p. 1-2). Further WO ‘919 teaches treatment can include a second therapeutic agent such as a PPAR-alpha agonist, pemafibrate, which corresponds to (R)-2-[3-[[N-(benzoxazole-2-yl)-N-3-(4-methoxyphenoxy)propyl]aminomethyl]phenoxy]butyric acid (the compound of instant claim 9), or bempodoic acid (ETC-1002), which corresponds to 8-hydroxy-2,2,14, 14-tetramethylpentadecanedioic acid (the compound of instant claim 10), - see paragraph [00154], p. 22-23, and the second therapeutic agent(s) can be combined with the glycine tripeptide molecule, in particular for a synergistic enhancement of activity (see paragraph [00182], p. 31). Thus WO ‘919 teaches the compounds pemafibrate or bempodoic acid (ETC-1002) in treating a metabolic disease and/or cardiovascular disease, wherein a metabolic and cardiovascular disease includes arteriosclerosis, hyperlipidemia which may be hypertriglyceridemia or hypercholesterolemia as WO ‘919 states that the secondary therapeutic agents used for control of dyslipidemia, diabetes and cardiovascular diseases associated with atherosclerosis are well known in the art and may be used in combination (see paragraph [00183], p. 31).
Thus, prior to the filing of the instant application, following the teachings of WO ‘919, it would have been prima facie obvious to combine the compounds bempedoic acid and pemafibrate in order to treat hypercholesterolemia or hypertriglyceridemia and/or arteriosclerosis. MPEP 2144.06, Section I states that it is obvious to combine equivalents known for the same purpose. "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted) (Claims to a process of preparing a spray-dried detergent by mixing together two conventional spray-dried detergents were held to be prima facie obvious.). (That the two claimed types of active agents, GABA-a agonists and ARBs, were known to be useful for the same purpose—alleviating hypertension—alone can serve as a motivation to combine). In the instant case, both bempedoic acid and pemafibrate are taught as agents for treating a metabolic disease and/or cardiovascular disease, wherein a metabolic and cardiovascular disease includes arteriosclerosis, hyperlipidemia which may be hypertriglyceridemia or hypercholesterolemia and for synergistic enhancement of said activity.
Conclusion
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KAREN CHENG whose telephone number is (703)756-4699. The examiner can normally be reached M-F, 9AM-6PM PST.
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/KAREN CHENG/Primary Examiner, Art Unit 1623
/ANAND U DESAI/Supervisory Patent Examiner, Art Unit 1655
